International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 25 - DOES OVEREXPRESSION OF THE IMPRINTED GENE NEURONATIN CAUSE A REDUCTION IN PITUITARY SIZE AND GROWTH HORMONE CELL NUMBERS?

Beechey C V
MRC Mammalian Genetics Unit

Co-Authors: 1) Peters J, 1) Skinner J, 2) Christian H, 3) Fischer-Colbrie R
Institutions: 1) MRC Mammalian Genetics Unit, 2) University of Oxford, 3) University of Innsbruck

Mouse distal Chromosome 2 has two imprinting regions, one containing a single imprinted gene, Nnat, and a more distal region containing the Gnas imprinting cluster. Uniparental inheritance of the more distal region causes morphological and behavioural abnormalities and early neonatal lethality. Uniparental inheritance of the more proximal region appeared to have relatively little effect on phenotype. The only effect that had been found previously was decreased folding of the cerebellum when this region is exclusively maternally derived (maternal duplication, MatDp). This effect was attributed to lack of expression of neuronatin, Nnat, because this gene shows no expression from the maternally derived allele and is expressed exclusively from the paternally derived allele. We have now found an effect on the pituitary when the Nnat region is solely paternally derived. Thus mice with two paternally derived copies of the region (paternal duplication, PatDp) and therefore two expressed copies of Nnat have small pituitaries. Estimates of pituitary area were obtained from digital photographs using imaging software. The pituitary area in PatDps was significantly smaller, typically 47% to 76% of the area found in normal sibs. Growth hormone cells were reduced in number and size. Pituitary area in MatDp mice is similar to that in normal sibs. The results suggest that the small pituitary is due to overexpression of Nnat


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